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Residual Solvents in Nanomedicine and Lipid-Based Drug Delivery Systems: a Case Study to Better Understand Processes

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Abstract

Purpose

Complexities surrounding the manufacture and quality control of nanomedicines become increasingly apparent. This research article offers a case study to investigate how, at the laboratory scale, various stages of liposome and nanoparticle synthesis affect the amount of residual solvent found in the formulations. The objective is to bring insights on the reliability of each of these processes to provide final products which meet regulatory standards and facilitate identifying possible bottleneck early during the development process.

Methods

The residual solvent at various stages of preparation and purification was measured by headspace gas chromatography. Liposomes were prepared by two different methods with and without solvent. Polymer nanoparticles prepared via nanoprecipitation and purified by ultrafiltration were studied. The effects of purification by size exclusion chromatography and dialysis were also investigated.

Results

The complete removal of residual solvent requires processes which go beyond usual preparation methods.

Conclusions

This work might prove valuable as a reference for scientists of different fields to compare their own practices and streamline the translation of nanomedicines into efficacious and safe drug products.

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Author notes

    Authors and Affiliations

    1. Faculty of Pharmacy, Université Laval, Pavillon Ferdinand-Vandry, 1050, avenue de la Médecine, Québec, G1V 0A6, Canada

      Amrita Dikpati & Nicolas Bertrand

    2. Endocrinology and Nephrology Unit, CHU de Québec - Université Laval Research Center, 2705 Laurier Blvd, Québec City, G1V 4G2, Canada

      Amrita Dikpati, Farzad Mohammadi, Karine Greffard, Caroline Quéant, Iwona Rudkowska & Nicolas Bertrand

    3. Department of Kinesiology, Faculty of Medicine, Université Laval, 2300 rue de la Terrasse, Québec, G1V 0A6, Canada

      Farzad Mohammadi & Iwona Rudkowska

    4. Faculté de Pharmacie de Paris, Université de Paris, 4 avenue de l’Observatoire, 75006, Paris, France

      Philippe Arnaud

    5. Micro et Nanomédecines Translationnelles, MINT, UNIV Angers, UMR INSERM 1066, UMR CNRS 6021, 4 rue Larrey, 49933, Angers, Cedex 9, France

      Guillaume Bastiat

    Authors
    1. Amrita Dikpati
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    8. Nicolas Bertrand
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    Contributions

    NB designed the experiments. AD, FM, KG, CQ, PA and NB conducted the experiments and analyzed the results. NB prepared the figures and wrote the manuscript. GB, IR, NB contributed methods, funding and/or infrastructures. All authors read and commented the manuscript.

    Corresponding author

    Correspondence to Nicolas Bertrand.

    Additional information

    Amrita Dikpati, Farzad Mohammadi and Karine Greffard contributed equally to this work.

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    Dikpati, A., Mohammadi, F., Greffard, K. et al. Residual Solvents in Nanomedicine and Lipid-Based Drug Delivery Systems: a Case Study to Better Understand Processes. Pharm Res 37, 149 (2020). https://doi.org/10.1007/s11095-020-02877-x

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    • DOI: https://doi.org/10.1007/s11095-020-02877-x

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